N6-methyladenine in DNA antagonizes SATB1 in early development.

The recent discovery of N6-methyladenine (N6-mA) in mammalian genomes suggests that it may serve as an epigenetic regulatory mechanism1. However, the biological role of N6-mA and the molecular pathways that exert its function remain unclear. Here we show that N6-mA has a key role in changing the epigenetic landscape during cell fate transitions in early development. We found that N6-mA is upregulated during the development of mouse trophoblast stem cells, specifically at regions of stress-induced DNA double helix destabilization (SIDD)2-4. Regions of SIDD are conducive to topological stress-induced unpairing of the double helix and have critical roles in organizing large-scale chromatin structures3,5,6. We show that the presence of N6-mA reduces the in vitro interactions by more than 500-fold between SIDD and SATB1, a crucial chromatin organizer that interacts with SIDD regions. Deposition of N6-mA also antagonizes SATB1 function in vivo by preventing its binding to chromatin. Concordantly, N6-mA functions at the boundaries between euchromatin and heterochromatin to restrict the spread of euchromatin. Repression of SIDD-SATB1 interactions mediated by N6-mA is essential for gene regulation during trophoblast development in cell culture models and in vivo. Overall, our findings demonstrate an unexpected molecular mechanism for N6-mA function via SATB1, and reveal connections between DNA modification, DNA secondary structures and large chromatin domains in early embryonic development.

Quantification of the Androgen and Estrogen Receptors in the Penile Tissues of Hypospadias in Comparison with Normal Children.

INTRODUCTION: Hypospadias is a common congenital abnormality typified by a proximally placed ectopic urethral meatus along the ventral surface of the penis. Androgen receptor (AR) and estrogen receptor (ER) expression in the hypospadias tissues may be altered in hypospadias. METHODOLOGY: We evaluated by immunohistochemistry the AR and ER expression in 75 tissues from hypospadias repair, and compared this expression to that of tissue from 75 patients undergoing circumcision. We also compared the intensity of AR and ER expression between different severities of hypospadias. RESULTS: AR quantitative grading score decreased with severity of hypospadias, while the ER score increased as the hypospadias worsened, which was statistically significant (p-value <0.05). CONCLUSION: The penile tissue AR expression is decreased and ER expression is increased with increasing severity of hypospadias.

Assessing the Feasibility of Predicting Intermediate Outcomes of Esophageal Atresia Using Okamoto Classification: A Prospective Study.

Purpose: Several risk classifications based on various preoperative factors have been proposed to prognosticate the immediate survival of children operated for esophageal atresia. A major drawback of these classifications is that they only focus on immediate survival while ignoring the long-term morbidity and mortality in these children. Our study aims to bridge this gap in knowledge by studying the impact of one such classification (Okamoto's classification) on mortality and morbidity during a period of 1 year after discharge from the hospital in operated cases of esophageal atresia. Materials and Methods: After institutes ethical clearance, 106 children operated for esophageal atresia-tracheoesophageal fistula between 2012 and 2015 were studied prospectively for a period of 1 year after their discharge. The children were graded as per Okamoto classification. The primary objective was to determine the efficacy of this classification in predicting the survival rates in infancy and the secondary objective was to compare the complication rates in these children based on the classification. Results: Sixty-nine children met the inclusion criteria. There were 40, 15, 10, and 4 children in Okamoto Classes I, II, III, and IV, respectively. Twenty-one patients (30%) died during the follow-up period with the maximum number of deaths occurring in Okamoto Class IV (75%) and the minimum in Okamoto Class I (17.5%) (P = 0.003). There was a significant correlation between the Okamoto classes with the incidence of poor weight gain (P = 0.001), lower respiratory tract infection (P = 0.007), and failure to thrive (P = 0.01) higher in Okamoto IV and III as compared to I and II. Conclusion: Okamoto prognostic classification during the initial hospitalization is relevant even at 1 year follow-up with increased mortality and morbidity in Okamoto Class IV as compared to Class I.

Recurrent tracheo-esophageal fistula- management challenges: Case report and review of current literature.

Recurrent tracheoesophageal fistula is a rare complication of esophageal atresia surgery with an incidence of 3-15%. The presentation is subtle and is often missed, presenting as choking episodes during feed and recurrent chest infections. It is both a diagnostic and management challenge and requires a dedicated multidisciplinary pediatric surgical setup with adequate infrastructure for optimal management. We present a case of recurrent tracheoesophageal fistula which was diagnosed at our center. The patient underwent successful surgical management and is thriving well at six months follow-up period.

Acupuncture-D" - Bilateral Pneumothoraces Following Dry Needling.

Presentation A 24-year-old newly graduated junior doctor presented to the emergency department with acute onset chest pain, haemoptysis and exertional dyspnoea following a dry needling session. Diagnosis Chest x-ray showed bilateral pneumothoraces, worse on the right side. Treatment The bilateral pneumothoraces were treated conservatively with supplemental oxygen initially. On the second day of admission, repeat chest x-ray demonstrated a worsening right sided pneumothorax. While vitally stable, the patient however had become increasingly dyspnoeic, and a needle aspiration was performed on the right side with good effect. Conclusion The anatomical location targeted along with the patients low-normal BMI makes her high-risk when considering the skin-to-pleura distance. Although the incidence of pneumothorax is low, it is imperative that we improve awareness both for the treating physician and the diagnosing clinician. We must begin to fill the distinct lack in available literature surrounding the potential adverse effects of dry needling.

Antenatally Detected Functional Adrenocortical Adenoma: A Case Report and Review of Current Literature.

Pediatric adrenocortical tumors (ACTs) are rare entities with an incidence of 0.2% of all pediatric tumors. Only two cases of antenatally detected ACT have been reported in the literature. Our case is the first report of an antenatally detected suprarenal mass which manifested with postnatal virilizing features and was proven to be adrenocortical adenoma on histology.

When Fryn met Edward: Two rare syndromes in a single patient.

A neonate born at our centre was diagnosed as Fryns Syndrome ie congenital diaphragmatic hernia with facial dysmorphism and distal limb anomalies, which is a rare disorder with only a few hundred cases reported till date.With high clinical index of suspicion and further evaluation, the diagnosis was confirmed. The baby was initially stabilized and later underwent repair of the diaphragmatic hernia. Despite best measures, the baby could not be salvaged. When severe, this can be lethal and diagnosis can only be made after autopsy. However, with early suspicion, better modalities of investigations available and improved NICU care, these babies can be salvaged. We report a case of Fryns Syndrome who was incidentally found to have Edward Syndrome as well. Such an extremely rare combination is yet to be reported in medical literature.Also with updated genetic studies, better diagnostics and treatment options coming up in future, there are chances to improve the survivability of these babies. It is prudent to document all such cases to aid in better understanding of the disease process.

Use of therapeutic caffeine in acute care postoperative and critical care settings: a scoping review.

BACKGROUND: Caffeine is the most utilised psychoactive drug worldwide. However, caffeine withdrawal and the therapeutic use of caffeine in intensive care and in the perioperative period have not been well summarised. Our objective was to conduct a scoping review of caffeine withdrawal and use in the intensive care unit (ICU) and postoperative patients. METHODS: PubMed, Embase, CINAHL Complete, Scopus and Web of Science were systematically searched for studies investigating the effects of caffeine withdrawal or administration in ICU patients and in the perioperative period. Areas of recent systematic review such as pain or post-dural puncture headache were not included in this review. Studies were limited to adults. RESULTS: Of 2268 articles screened, 26 were included and grouped into two themes of caffeine use in in the perioperative period and in the ICU. Caffeine withdrawal in the postoperative period increases the incidence of headache, which can be effectively treated prophylactically with perioperative caffeine. There were no studies investigating caffeine withdrawal or effect on sleep wake cycles, daytime somnolence, or delirium in the intensive care setting. Administration of caffeine results in faster emergence from sedation and anaesthesia, particularly in individuals who are at high risk of post-extubation complications. There has only been one study investigating caffeine administration to facilitate post-anaesthetic emergence in ICU. Caffeine administration appears to be safe in moderate doses in the perioperative period and in the intensive care setting. CONCLUSIONS: Although caffeine is widely used, there is a paucity of studies investigating withdrawal or therapeutic effects in patients admitted to ICU and further novel studies are a priority.

Klippel Feil syndrome with crossed fused renal ectopia with pelviureteric junction obstruction: A rare association.

An 11-year-old female patient presented with congenital spinal deformity with a history of occasional pain in the right flank for a duration of six months. On evaluation, she was diagnosed to be a case of type III Klippel Feil syndrome (KFS) with crossed fused renal ectopia (left to right) and pelviureteric junction obstruction (PUJO) of the right moiety. The patient underwent successful pyeloplasty of the right moeity. To the best of our knowledge, this is the first reported case in the literature with a combination of KFS, crossed fused renal ectopia, and PUJO.

Common cloaca: An uncommon entity posing diagnostic and management challenges: Our experience with nine cases.

BACKGROUND: Cloacal anomalies are the severest and most complex of all anorectal malformations (ARMs). They require careful evaluation and meticulous surgery tailored to suit each variant. We present our experience in a series of nine cases. METHODS: This includes a retrospective review of 9 cases of cloaca managed at a tertiary care centre between 2015 and 2019. RESULTS: Associated anomalies were seen in 44% cases. The definitive surgery was performed at a mean age of 15.2 months (10 months-19 months), the definitive surgery being rectal separation with total urogenital mobilisation. The common channel as measured during panendoscopy was up to 3 cm in 7 patients (78%), and only 2 patients had a common channel of more than 3 cm (22%). Of the 34 procedures that these nine patients underwent, there were four complications (12%). The median follow-up period after stoma closure was 18 months (5-32 months), and the mean age at last follow-up was 38 months (22-48 months). Five children (63%) had spontaneous voiding and remained dry in the intervening period. Three patients (37%) had poor urinary stream with dribbling and high postvoid residue requiring clean intermittent catheterisation. Six patients had faecal soiling (66%); four had daily soiling; and two had occasional soiling. Four patients had constipation (44%). Seven patients (77%) required daily enemas for bowel evacuation and to remain dry. CONCLUSION: Cloacal anomalies are rare and complex ARMs. Satisfactory urinary and bowel continence rates can be achieved even in these complex anomalies.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).

Barriers and prospects of India's conditional cash transfer program to promote institutional delivery care: a qualitative analysis of the supply-side perspectives.

BACKGROUND: Under the National Health Mission (NHM) of India, Janani Suraksha Yojana (JSY) offers conditional cash transfer and support services to pregnant women to use institutional delivery care facilities. This study aims to understand community health workers' (ASHAs) and program officials' perceptions regarding barriers to and prospects for the uptake of facilities offered under the JSY. METHODS: Fifty in-depth interviews of a purposively selected sample of ASHAs (n = 12), members of Village Health and Sanitation Committees (n = 11), and officials at different tiers of healthcare facilities (n = 27) were conducted in three Indian states. The data were analyzed thematically using ATLAS.ti software. RESULTS: Although the JSY has triggered considerable advancement on the Indian maternal and child health front, there are several barriers to be resolved pertaining to i) delivering quality care at health-facility; ii) linkages between home and health-facility; and iii) the community/household context. At the facility level, respondents cited an inability to treat birth complications as a barrier to JSY uptake, resulting in referrals to other (mostly private) facilities. Despite increased investment in health infrastructure under the program, shortages in emergency obstetric-care facilities, specialists and staff, essential drugs, diagnostics, and necessary equipment persisted. Weaker linkages between various vertical (standalone) elements of maternal and primary healthcare programs, and nearly uniform resource allocation to all facilities irrespective of caseloads and actual need also constrained the provision of quality healthcare. Barriers affecting the linkages between home and facility arose mainly due to the mismatch between the multiple demands and the availability of transport facilities, especially in emergency situations. Regarding community/household context, several socio-cultural issues such as resistance towards the ASHA's efforts of counselling, particularly from elderly family members, often adversely affected people's decision to seek healthcare. CONCLUSION: Adequate interventions at the community level, capacity building for healthcare providers, and measures to address underlying structural and systemic barriers are needed to improve the uptake of institutional maternal healthcare.

Developing the National Knowledge Platform in India: a policy and institutional analysis.

BACKGROUND: The importance of strong engagement between researchers and decision-makers in the improvement of health systems is increasingly being recognised in low- and middle-income countries (LMICs). In 2013, in India, the Ministry of Health and Family Welfare began exploring the formation of a National Knowledge Platform (NKP) for guiding and supporting public health and health systems research in the country. The development of the NKP represents an important opportunity to enhance the linkage between policy-makers and researchers from the health policy and systems research field in India. However, the development process also reflects the highly complex reality of policy-making in the Indian health sector. Our objective is to provide insight into the policy-making process for establishing a health sector knowledge platform in India, and in doing so, to analyse the enabling contextual factors, the interests and actions of stakeholders, and the varying institutional arrangements explored in the development of the NKP. METHODS: We used a qualitative case study methodology, conducting 16 in-depth interviews and reviewing 42 documents. We utilised General Thematic Analysis to analyse our data. Our research team combined perspectives from both outsiders (independent researchers with no prior or current involvement with the policy) and insiders (researchers involved in the policy-making process). RESULTS: We found that enabling contextual factors, and a combination of government and non-governmental stakeholders with core interests in public health and health systems, were able to gain considerable momentum in moving the idea for the NKP forward. However, complex evidence-to-policy processes in the Indian health sector resulted in complications in determining the right institutional arrangement for the platform. Establishing the appropriate balance between legitimacy and independence, as well as frequent changes in institutional leadership, were found to be additional issues that stakeholders contended with in building the NKP. CONCLUSION: As interest in platforms linking health sector policy-makers and researchers grows in LMICs, our findings may allow stakeholders to learn from the Indian experience thus far, and to anticipate some of the facilitators and barriers that could potentially arise in establishing such mechanisms.

Sixty years of Neurosurgery at Andhra Medical College and King George Hospital, Visakhapatnam: The (hi) story of the department.

The trials and trepidations of an emerging department, uncertainties of its survival midway through its course, the innovative ideas that initiated its development, a regimental discipline, addition of newer technological advances with changing times, and its blossoming as the one of the best departments in the region, mark the origin and development of the Department of Neurosurgery at Andhra Medical College (AMC) and King George Hospital (KGH) Visakhapatnam. AMC and KGH are getting ready to celebrate their centenary in 2023. This history of the department is derived from the knowledge of the immense effort and academic discipline that was required to bring it to its current stature. Dr. Sunkara Balaparameswara Rao (SBP Rao) established the Neurosurgical Unit at the AMC and the KGH, Visakhapatnam on 2nd April 1956. He has had the unique privilege of witnessing the entire history of the department, from the inception till today, which represents 60 years of continuous progress of the department after its establishment. He also took a very active role in organizing its Diamond Jubilee function held on 23rd September 2016. The first author of this article has also had the privilege of witnessing and being a part of the history of the department during the past half a century. This is a narration of what may be better termed 'the (hi) story of 60 years of Neurosurgery at AMC and KGH', Visakhapatnam, India.

A cross-sectional study of dentine sensitivity in periodontitis patients in Trinidad and Tobago.

OBJECTIVE: This cross-sectional study aimed to determine the prevalence, distribution and associated factors of dentine sensitivity (DS) among periodontitis patients in Trinidad. METHODS: Sequential patients meeting the periodontitis criteria (BPE 4/4*) were included and completed a questionnaire on DS prior to a full periodontal examination. Clinically elicited symptoms of DS and presence of cervical tooth wear were recorded. RESULTS: DS prevalence was 73.1% (n = 130; mean age 50 years). Mean number of sensitive teeth increased with increased severity of gingival recession. Most common initiating factors of DS were cold stimuli (70.5%), brushing (25.3%) and sour food (11.6%). Correlations were obtained for DS and race, toothbrush texture hardness, cervical tooth wear and gingival recession severity (P < 0.05; binary logistic regression). Cervical tooth wear was recorded in 46.3% of DS patients. Full-mouth plaque scores (FMPS) and full-mouth bleeding scores (FMBS) were statistically significantly (P < 0.05; Mann-Whitney U) test lower for DS versus non-DS patients. Patients reported a low usage (27.4%) and satisfaction (53.8%) rating for desensitizing agents. CONCLUSIONS: The high prevalence of DS was comparable to other studies on periodontitis patients. Progressive periodontal disease and toothbrush abrasion were possible aetiological factors for DS in this study. Knowledge of local dietary practices and the role of acidic (sour) foods in eliciting DS may aid in management. The high prevalence of cervical tooth wear and the lower FMPS and FMBS among DS patients may reflect more aggressive tooth brushing. DS does not seem to be a limitation to plaque control in DS versus non-DS patients in this study.

Sex and race and/or ethnicity differences in patients undergoing radiofrequency ablation for Barrett's esophagus: results from the U.S. RFA Registry.

BACKGROUND: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA). OBJECTIVE: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE. DESIGN: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE. PATIENTS: Patients enrolled with BE. INTERVENTIONS: RFA. MAIN OUTCOME MEASUREMENTS: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, and number of treatments to CEIM by sex and race and/or ethnicity. RESULTS: Among 5521 patients (4052 men; 5126 white, 137 Hispanic, 82 African American, 40 Asian, 136 heritage not identified), women were younger (60.0 vs 62.1 years) and had shorter BE segments (3.2 vs 4.4 cm) and less dysplasia (37% vs 57%) than did men. Women were almost twice as likely to stricture (odds ratio 1.7; 95% confidence interval, 1.2-2.3). Although white patients were predominantly male, about half of African Americans and Asians with BE were female. African Americans and Asians had less dysplasia than white patients. Asians and African Americans had more strictures than did white patients. There were no sex or race differences in efficacy. LIMITATIONS: Observational study with non-mandated paradigms, no central laboratory for reinterpretation of pathology. CONCLUSION: In the U.S. RFA patient registry, women had shorter BE segments and less-aggressive histology. The usual tendency toward BE in men was absent in African Americans and Asians. Posttreatment stricture was more common among women and Asians. RFA efficacy did not differ by sex or race.

Surgical versus non-surgical interventions in people with adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine. While AIS can progress during growth and cause a surface deformity, it is usually not symptomatic. However, if the final spinal curvature surpasses a certain critical threshold, the risk of health problems and curve progression is increased. Interventions for the prevention of AIS progression include scoliosis-specific exercises, bracing, and surgery. The main aims of all types of interventions are to correct the deformity and prevent further deterioration of the curve and to restore trunk asymmetry and balance, while minimising morbidity and pain, allowing return to full function. Surgery is normally recommended for curvatures exceeding 40 to 50 degrees to stop curvature progression with a view to achieving better truncal balance and cosmesis. Short-term results of the surgical treatment of people with AIS demonstrate the ability of surgery to improve various outcome measures. However there is a clear paucity of information on long-term follow-up of surgical treatment of people with AIS. OBJECTIVES: To examine the impact of surgical versus non-surgical interventions in people with AIS who have severe curves of over 45 degrees, with a focus on trunk balance, progression of scoliosis, cosmetic issues, quality of life, disability, psychological issues, back pain, and adverse effects, at both the short term (a few months) and the long term (over 20 years). SEARCH METHODS: We searched the Cochrane Back Review Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, four other databases, and three trials registers up to August 2014 with no language limitations. We also checked the reference lists of relevant articles and conducted an extensive handsearch of the grey literature. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and prospective controlled trials comparing spinal fusion surgery with non-surgical interventions in people with AIS with a Cobb angle greater than 45 degrees. We were interested in all types of instrumented surgical interventions with fusion that aimed to provide curve correction and spine stabilisation. DATA COLLECTION AND ANALYSIS: We found no RCTs or prospective controlled trials that met our inclusion criteria. MAIN RESULTS: We did not identify any evidence comparing surgical to non-surgical interventions for AIS with severe curves of over 45 degrees. AUTHORS' CONCLUSIONS: We cannot draw any conclusions.

Submerged anaerobic membrane bioreactor for wastewater treatment and energy generation.

Compared with conventional wastewater treatment processes, membrane bioreactors (MBRs) offer several advantages including high biodegradation efficiency, excellent effluent quality and smaller footprint. However, it has some limitations on account of its energy intensive operation. In recent years, there has been growing interest in use of anaerobic membrane bioreactors (AnMBRs) due to their potential advantages over aerobic systems, which include low sludge production and energy generation in terms of biogas. The aim of this study was to evaluate the performance of a submerged AnMBR for the treatment of synthetic wastewater having 4,759 mg/l chemical oxygen demand (COD). The COD removal efficiency was over 95% during the performance evaluation study. Treated effluent with COD concentration of 231 mg/l was obtained for 25.5 hours hydraulic retention time. The obtained total organic carbon concentrations in feed and permeate were 1,812 mg/l and 89 mg/l, respectively. An average biogas generation and yield were 25.77 l/d and 0.36 m3/kg COD, respectively. Evolution of trans-membrane pressure (TMP) as a function of time was studied and an average TMP of 15 kPa was found suitable to achieve membrane flux of 12.17 l/(m2h). Almost weekly back-flow chemical cleaning of the membrane was found necessary to control TMP within the permissible limit of 20 kPa.